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European Journal of Drug Metabolism and Pharmacokinetics

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https://www.readbyqxmd.com/read/30229398/longitudinal-pharmacokinetics-of-mycophenolic-acid-in-elderly-renal-transplant-recipients-compared-to-a-younger-control-group-data-from-the-neverold-trial
#1
Paschoalina Romano, Fabiana Agena, Pérsio de Almeida Rezende Ebner, Nairo Massakazu Sumita, Ana Heloísa Kamada Triboni, Fernanda Ramos, Márcio Dos Santos Garcia, Nilo José Coelho Duarte, Francine Brambate Carvalhinho Lemos, Nelson Zocoler Galante, Elias David-Neto
BACKGROUND AND OBJECTIVES: Elderly patients are increasingly likely to be recipients of transplants. However, the pharmacokinetics of mycophenolic acid (MPA) in this population are yet to be studied in detail. The objective of this study was to assess whether there were differences in MPA pharmacokinetic parameter values between elderly recipients and younger-adult recipients during the 6 months immediately following renal transplantation. METHODS: In this analysis, the longitudinal 12-h pharmacokinetics of MPA, administered as enteric-coated mycophenolate sodium (EC-MPS), were evaluated in 44 elderly renal transplant recipients and compared with the corresponding pharmacokinetics of MPA in 31 younger adult recipients...
September 18, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30225640/determination-of-the-pharmacokinetics-and-tissue-distribution-of-methyl-3-4-dihydroxybenzoate-mdhb-in-mice-using-liquid-chromatography-tandem-mass-spectrometry
#2
Jia Hui Wang, Song Hui Hu, Ji Yan Su, Jun Ping Pan, Xiang Nan Mi, Hai Ju Geng, Wei Zhang, Liang Cai, Chao Fen Su, Ai Hua Hong, Huan Min Luo
BACKGROUND AND OBJECTIVES: Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work aims to reveal the pharmacokinetics and tissue distribution characteristics of MDHB. METHODS: The pharmacokinetics and tissue distribution of MDHB were analyzed using LC-MS/MS after a single intragastric administration (50 to 450 mg/kg) in mice, and samples were collected from five animals at specific time points. RESULTS: Pharmacokinetic parameters of MDHB following intragastric administrations were: the time to peak concentration (Tmax ) ranged from 0...
September 17, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30209794/pharmacokinetics-and-bioavailability-enhancement-of-baicalin-a-review
#3
REVIEW
Ting Huang, Yanan Liu, Chengliang Zhang
Baicalin is one of the major bioactive components of Scutellaria radix, a Chinese herb that has been used since ancient times. Baicalin has various pharmacological activities, including antitumor, antimicrobial, and antioxidant, and has wide clinical applications. Baicalin displays a distinct pharmacokinetic profile including gastrointestinal hydrolysis, enterohepatic recycling, carrier-mediated transport, and complicated metabolism. The in vivo disposition of baicalin is affected by combinations of other herbs and baicalin can interact with other co-administered drugs due to competition between metabolic enzymes and protein binding...
September 12, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30209793/intestinal-absorption-of-isoalantolactone-and-alantolactone-two-sesquiterpene-lactones-from-radix-inulae-using-caco-2-cells
#4
Renjie Xu, Ying Peng, Mengyue Wang, Xiaobo Li
BACKGROUND: Isoalantolactone and alantolactone are the main sesquiterpene lactones in Radix Inulae (dried root of Inula helenium L. or I. racemosa Hook. F.), which is a frequently utilized herbal medicine. They also occur in several plants and have various pharmacologic effects. However, they have been found to have poor oral bioavailability in rats. OBJECTIVES: To understand the intestinal absorptive characteristics of isoalantolactone and alantolactone as well specific influx and efflux transporters in their absorption...
September 12, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30206814/correction-to-evaluation-of-generic-methods-to-predict-human-pharmacokinetics-using-physiologically-based-pharmacokinetic-model-for-early-drug-discovery-of-tyrosine-kinase-inhibitors
#5
Hong-Can Ren, Yang Sai, Tao Chen
The original version of this article unfortunately contained a mistake. Conflict of interest statement was incorrect. The corrected COI statement is given below.
September 11, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30187443/the-influence-of-diabetes-mellitus-on-glucuronidation-and-sulphation-of-paracetamol-in-patients-with-febrile-neutropenia
#6
Anna Stachowiak, Edyta Szałek, Agnieszka Karbownik, Anna Łojko, Joanna Porażka, Iwona Przewoźna, Tomasz Grabowski, Anna Wolc, Edmund Grześkowiak
BACKGROUND AND OBJECTIVES: Numerous studies have confirmed the influence of diabetes mellitus on the pharmacokinetics of drugs. Paracetamol (APAP) is an antipyretic that is commonly used in febrile neutropenia (FN) therapy. APAP is chiefly metabolised by glucuronidation and sulphation. This study assessed the influence of diabetes on the pharmacokinetics of paracetamol and its metabolites: glucuronide (APAP-glu) and sulfate (APAP-sulfate) in FN patients. METHODS: Patients with FN received single intravenous dose 1000 mg of APAP...
September 5, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30168000/impact-of-efavirenz-metabolism-on-loss-to-care-in-older-hiv-africans
#7
Jessie Torgersen, Scarlett L Bellamy, Bakgaki Ratshaa, Xiaoyan Han, Mosepele Mosepele, Athena F Zuppa, Marijana Vujkovic, Andrew P Steenhoff, Gregory P Bisson, Robert Gross
BACKGROUND AND OBJECTIVE: Efavirenz is commonly used in Africa and is frequently associated with neurocognitive toxicity, which may compromise clinical outcomes. Older individuals are at increased risk for drug toxicity and clinical outcomes may be worse in older age, particularly among those individuals with cytochrome P450 (CYP) 2B6 polymorphisms associated with slower efavirenz metabolism. The aim of this study was to determine if the CYP2B6 polymorphisms differentially impacts loss to care in older people...
August 30, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30167999/evaluation-of-drug-biliary-excretion-using-sandwich-cultured-human-hepatocytes
#8
REVIEW
Olivier Fardel, Amélie Moreau, Marc Le Vée, Claire Denizot, Yannick Parmentier
Evaluation of hepatobiliary transport of drugs is an important challenge, notably during the development of new molecular identities. In this context, sandwich-cultured human hepatocytes (SCHH) have been proposed as an interesting and integrated tool for predicting in vitro biliary excretion of drugs. The present review was therefore designed to summarize key findings about SCHH, including their establishment, their main functional features and their use for the determination of canalicular transport and the prediction of in vivo biliary clearance and hepatobiliary excretion-related drug-drug interactions...
August 30, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30167998/clinical-pharmacokinetics-and-pharmacodynamics-of-direct-oral-anticoagulants-in-patients-with-renal-failure
#9
REVIEW
Roberto Padrini
A recent survey on the use of direct oral anticoagulants (DOACs) revealed that 43% of patients with atrial fibrillation and renal impairment were potentially overdosed and had a hazard ratio for major bleeding of 2.19. In this review, we analyse and discuss the effect of renal failure on the pharmacokinetics and pharmacodynamics of DOACs and of strategies proposed to adjust doses according to the level of renal dysfunction. The pharmacokinetic characteristics of available DOACs (dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban) differ substantially as regards oral bioavailability, plasma protein binding and the relative involvement of renal and non-renal elimination...
August 30, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30159654/effect-of-cyp2c9-polymorphisms-on-the-pharmacokinetics-of-indomethacin-during-pregnancy
#10
Mansi Shah, Meixiang Xu, Poonam Shah, Xiaoming Wang, Shannon M Clark, Maged Costantine, Holly A West, Tatiana N Nanovskaya, Mahmoud S Ahmed, Sherif Z Abdel-Rahman, Raman Venkataramanan, Steve N Caritis, Gary D V Hankins, Erik Rytting
BACKGROUND AND OBJECTIVE: Cytochrome P450 (CYP) 2C9 catalyzes the biotransformation of indomethacin to its inactive metabolite O-desmethylindomethacin (DMI). The aim of this work was to determine the effect of CYP2C9 polymorphisms on indomethacin metabolism in pregnant women. METHODS: Plasma concentrations of indomethacin and DMI at steady state were analyzed with a validated LC-MS/MS method. DNA was isolated from subject blood and buccal smear samples. Subjects were grouped by genotype for comparisons of pharmacokinetic parameters...
August 29, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30151746/simultaneous-determination-of-rivaroxaban-and-enalapril-in-rat-plasma-by-uplc-ms-ms-and-its-application-to-a-pharmacokinetic-interaction-study
#11
Shu Zheng, Shun-Bin Luo, Yi-Bin Mei, Jing Guo, Li-Jun Tong, Qiang Zhang, Xia-Yan Ye
BACKGROUND AND OBJECTIVES: There have been no animal experiments and clinical studies on the pharmacokinetic interaction between rivaroxaban and enalapril. To investigate whether a potential pharmacokinetic interaction is present between rivaroxaban and enalapril, a rapid and sensitive Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine the concentration of rivaroxaban and enalapril in rat plasma and was then applied to a pharmacokinetic interaction study...
August 27, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30136219/predicting-human-pharmacokinetics-physiologically-based-pharmacokinetic-modeling-and-in-silico-adme-prediction-in-early-drug-discovery
#12
Jian Shi, Weibin Zha
No abstract text is available yet for this article.
August 23, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30132264/biodistribution-and-pharmacokinetics-of-amblyomin-x-a-novel-antitumour-protein-drug-in-healthy-mice
#13
Pamela Boufleur, Juliana Mozer Sciani, Mauricio Goldfeder, Fernanda Faria, Vânia Branco, Ana Marisa Chudzinski-Tavassi
BACKGROUND: Amblyomin-X is a recombinant protein under development for cancer treatment owing to its selective cytotoxic activity over several tumour cell lines and tumour regression in mice models. The aim of this study was to examine the distribution and pharmacokinetics of amblyomin-X in healthy female mice. METHODS: Amblyomin-X was injected intravenously into the healthy animals and at controlled times plasma and organs were removed and analysed for identification and quantification of the protein...
August 21, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30105488/influence-of-orally-administered-borneol-on-the-expression-of-hepatic-transporters-in-rats
#14
Lin Chen, Lu Liao, Ting Zhai, Xiangtao Huang, Yong Chen
BACKGROUND AND OBJECTIVE: Borneol, a traditional Chinese medicine (TCM), is often orally co-administered with other TCM and chemical drugs, but the drug-drug interactions between borneol and the other compounds remains unclear. This work investigates the effect of orally administered borneol on the transcription and expression of hepatic uptake transporters (Ntcp, Oatp2b1, Oatp1a1, Oatp1a4, Oct1, Oct2, Octn2 and Oat2) and efflux transporters (Mdrla, Mrp2, Mrp4 and Mrp5) in rats, aiming to obtain essential information to guide its clinical applications...
August 13, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30047107/clinical-pharmacokinetics-and-drug-interactions-of-doravirine
#15
Kyle John Wilby, Nesma Ahmed Eissa
Doravirine is a new HIV-1 non-nucleoside reverse transcriptase inhibitor that has demonstrated a good efficacy and safety profile in clinical trials. It has a therapeutic profile that makes it an attractive option for treatment of HIV-1 infection. As such, there has been an increase in the published literature regarding the pharmacokinetics of doravirine and potential for drug-drug interactions. This review aimed to identify pharmacokinetic literature pertaining to doravirine, used findings from the literature to summarize its pharmacokinetic profile, and finally evaluated literature describing actual and potential drug interactions...
July 25, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30039459/evaluation-of-generic-methods-to-predict-human-pharmacokinetics-using-physiologically-based-pharmacokinetic-model-for-early-drug-discovery-of-tyrosine-kinase-inhibitors
#16
Hong-Can Ren, Yang Sai, Tao Chen
BACKGROUND: Requirements for predicting human pharmacokinetics in drug discovery are increasing. Developing different methods of human pharmacokinetic prediction will facilitate lead optimization, candidate nomination, and dosing regimens before clinical trials at various early drug discovery stages. OBJECTIVES: To develop and validate generic methods of human pharmacokinetic prediction to meet the requirements in early drug discovery. METHODS: The physiologically based pharmacokinetic (PBPK) model implemented in Gastroplus™ was used for human pharmacokinetic predictions...
July 23, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30027304/reduced-clearance-of-phenobarbital-in-advanced-cancer-patients-near-the-end-of-life
#17
Hirokazu Nakayama, Hirotoshi Echizen, Ryuichi Ogawa, Takao Orii, Toshiaki Kato
BACKGROUND AND OBJECTIVES: Little is known about the pharmacokinetics of phenobarbital in terminally ill cancer patients. We investigated whether phenobarbital clearance alters depending on the length of survival. METHODS: We retrospectively reviewed the clinical, laboratory, and therapeutic drug monitoring (TDM) records of patients who received parenteral or oral phenobarbital for 21 consecutive days or longer between 2000 and 2016. Patients were divided into non-cancer and cancer groups...
July 19, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29956215/pharmacokinetics-of-tramadol-and-celecoxib-in-japanese-and-caucasian-subjects-following-administration-of-co-crystal-of-tramadol-celecoxib-ctc-a-randomised-open-label-study
#18
Helen Dooner, Gill Mundin, Sabine Mersmann, Carla Bennett, Ulrike Lorch, Mercedes Encabo, Marisol Escriche, Gregorio Encina, Kevin Smith
BACKGROUND AND OBJECTIVES: Co-Crystal of Tramadol-Celecoxib (CTC) is a first-in-class active pharmaceutical ingredient (API-API) co-crystal of rac-tramadol.HCl and celecoxib in a 1:1 molecular ratio (100 mg CTC: 44 mg rac-tramadol.HCl and 56 mg celecoxib). Tramadol and celecoxib pharmacokinetics are modified after CTC administration versus administration of reference products. This randomised, open-label, crossover, phase 1 study assessed CTC pharmacokinetics, dose proportionality, safety and tolerability in Japanese and Caucasian subjects...
June 28, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29943105/application-of-a-volumetric-absorptive-microsampling-device-to-a-pharmacokinetic-study-of-tacrolimus-in-rats-comparison-with-wet-blood-and-plasma
#19
Kenji Kita, Kenichi Noritake, Yuji Mano
BACKGROUND AND OBJECTIVES: Volumetric absorptive microsampling (VAMS) devices are useful for sampling a smaller volume of blood from rodents in the preclinical setting. In the present study, we evaluated the proof of concept of a VAMS device by comparing the pharmacokinetic data of tacrolimus in rats among dried blood in VAMS, wet blood, and plasma. METHODS: Tacrolimus was administered orally, to rats, at a dose of 10 mg/kg. Only 10 μL aliquots of blood were absorbed by VAMS devices at designated time points...
June 25, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30117069/animal-pharmacokinetic-pharmacodynamic-studies-apps-reporting-guidelines
#20
Jasbir Singh, Fawzy Elbarbry, Ke Lan, Tomasz Grabowski
Animal pharmacokinetic/pharmacodynamic studies are commonly used to provide meaningful preclinical information that can be utilized by the scientific community to conduct first-in-human studies. Poor presentation and interpretation of the data limit study reproducibility, and may result in rejection when the study is submitted to a journal, leading to loss of time and resources at multiple levels. In addition, inconsistencies in reporting the results of animal studies may limit the ability to extrapolate the experimental findings to humans...
October 2018: European Journal of Drug Metabolism and Pharmacokinetics
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